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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to examine the efficacy and safety of duloxetine, a balanced and potent dual reuptake inhibitor of serotonin and norepinephrine, in the management of diabetic peripheral neuropathic pain. Serotonin and norepinephrine are thought to inhibit pain via descending pain pathways. In a 12-week, multicenter, double-blind study, 457 patients experiencing pain due to polyneuropathy caused by Type 1 or Type 2 diabetes mellitus were randomly assigned to treatment with duloxetine 20 mg/d (20 mg QD), 60 mg/d (60 mg QD), 120 mg/d (60 mg BID), or placebo. The diagnosis was confirmed by a score of at least 3 on the Michigan Neuropathy Screening Instrument. The primary efficacy measure was the weekly mean score of the 24-h Average Pain Score, which was rated on an 11-point (0-10) Likert scale (no pain to worst possible pain) and computed from diary scores between two site visits. Duloxetine 60 and 120 mg/d demonstrated statistically significant greater improvement compared with placebo on the 24-h Average Pain Score, beginning 1 week after randomization and continuing through the 12-week trial. Duloxetine also separated from placebo on nearly all the secondary measures including health-related outcome measures. Significantly more patients in all three active-treatment groups achieved a 50% reduction in the 24-h Average Pain Score compared with placebo. Duloxetine treatment was considered to be safe and well tolerated with less than 20 percent discontinuation due to adverse events. Duloxetine at 60 and 120 mg/d was safe and effective in the management of diabetic peripheral neuropathic pain.
Pain 2005 Jul
PMID:Duloxetine vs. placebo in patients with painful diabetic neuropathy. 1592 94

The efficacy of duloxetine in the treatment of major depressive disorder in women of approximately perimenopausal age (40-55 years; 62 placebo subjects and 55 subjects taking duloxetine, 60 mg/day) was compared with that observed in cohorts of younger (<40 years, 94 placebo subjects and 85 duloxetine subjects) and older (>55 years, 26 placebo subjects and 25 duloxetine subjects) women. Women (ages 40-55 years) receiving duloxetine demonstrated significantly greater improvement in total scores on the 17-item Hamilton Rating Scale for Depression compared with placebo at the study endpoint (week 9). Significant advantages for duloxetine over placebo were observed on 17-item Hamilton depression scale subscales (core, Maier, anxiety, retardation, and sleep), in addition to the Clinical Global Impression severity and Patient Global Impression of Improvement Scale, the Quality of Life in Depression Scale, and Visual Analog Scales assessing pain severity. The magnitude of duloxetine's treatment effect in women ages 40-55 years was similar to that observed in younger (age <40 years) and older (age >55 years) female patients. In the placebo treatment groups, however, mean changes differed substantially by age group with the smallest placebo responses observed in the 40-55 age group. Duloxetine (60 mg/day) was demonstrated to be an effective treatment for major depressive disorder in this cohort of women ages 40-55 years.
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PMID:Duloxetine for the treatment of major depressive disorder in women ages 40 to 55 years. 1600 Jun 78

Chronic pain is among the most common conditions to initiate medical care; 40% of patients victimized by chronic pain are not under the supervision of a physician, and about 70% of patients with severe pain are receiving pain medical care. About dollar 100 billion is an annual estimated cost representing loss of productivity, increased medical costs, and income loss. Major depressive disorder is not infrequently encountered in daily clinical practice often presenting with somatic complaints that include varieties of pain, and these may be so prominent as to direct the treatment to the somatic complaint evaluation to the exclusion of underlying psychopathology. Anxiety disorders and other psychiatric disorders may also present with such a somatization evaluation focus. Serotonin noradrenergic reuptake inhibitors (SNRIs), ie, venlafaxine and duloxetine, offer benefits over tricyclic antidepressants and serotonin reuptake inhibitors. Years of experience with venlafaxine representing a first-line pharmacotherapy for depression and anxiety have benefited patients presenting with somatic symptoms with a robust onset. A more rapid achievement by venlafaxine of remission and a high-quality pharmacokinetic and pharmacodynamic profile lead to patient compliance and facilitate both fewer relapses and recurrences. Duloxetine is broadly discussed, revealing pharmacokinetic, pharmacodynamic, adverse/side effects, cautions with requisite patient-specific selection, and laboratory monitoring. The management of somatic pain complaints of physical and psychiatric origin is discussed.
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PMID:The role of venlafaxine and duloxetine in the treatment of depression with decremental changes in somatic symptoms of pain, chronic pain, and the pharmacokinetics and clinical considerations of duloxetine pharmacotherapy. 1614 29

Duloxetine is the first relatively balanced serotonin and noradrenaline re-uptake inhibitor to be widely available for three indications including: major depressive disorder, peripheral diabetic neuropathic pain and female stress urinary incontinence, although it is not currently approved for all indications in all countries. Generally, duloxetine is safe and well-tolerated across indications, with few reported serious side effects. Common adverse events are consistent with the pharmacology of the molecule and are mainly referable to the gastrointestinal and the nervous systems. The studied dose range is up to 400 mg/day (administered 200 mg b.i.d) but the maximum dose approved for marketing is 120 mg/day (administered 60 mg b.i.d). Duloxetine is eliminated (half-life = 12.1 hours) primarily in the urine after extensive hepatic metabolism by multiple oxidative pathways, methylation and conjugation. Duloxetine would not be expected to cause clinically significant inhibition of the metabolic clearance of drugs metabolised by P450 (CYP)3A, (CYP)1A2, (CYP)2C9, or (CYP)2C19, but would be expected to cause some inhibition of CYP 2D6. Duloxetine should not be used in combination CYP 1A2 inhibitors or nonselective, irreversible monoamine oxidase inhibitors. The purpose of this review is to provide an overview of some of the most important information related to safety and tolerability of duloxetine.
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PMID:Safety and adverse event profile of duloxetine. 1625 58

Duloxetine is a balanced serotonin noradrenaline re-uptake inhibitor that has recently become the first agent to receive regulatory approval for the treatment of painful diabetic neuropathy in the US. This compound has no other significant receptor or channel activities other than the serotonin and noradrenaline re-uptake inhibition mechanisms and works to diminish or control the symptoms of diabetic neuropathy. Duloxetine has no known neuroprotective or other effects that prevent the development of neuropathy in patients with diabetes. Its effectiveness in diabetic neuropathy confirms the proposed role of serotonin and noradrenaline as key mediators of the descending pain inhibition pathways of the brain stem and spinal cord. Clinical studies have demonstrated the high degree of safety and efficacy for the compound with no adverse effects on glycaemic control due to the action of duloxetine being identified.
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PMID:Duloxetine in diabetic neuropathy. 1643 85

Antidepressants that inhibit the re-uptake of serotonin and noradrenaline might offer a chance to reduce the multiple symptoms of depression, as both serotonin and noradrenaline seem to be responsible for the emotional and physical symptoms of depression. The potential superiority of a dual mechanism of action has already been demonstrated in a number of clinical trials. Duloxetine, a novel dual acting, selective serotonin and noradrenaline-re-uptake inhibitor, has demonstrated high remission rates and good efficacy on physical symptoms, especially painful physical symptoms of depression. The results from studies in diabetic neuropathic pain provide further evidence of the effect of duloxetine on pain, independent of its effect on depression. Therefore, duloxetine provides an alternative to current therapeutic options in the treatment of the different symptoms of depression.
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PMID:Duloxetine: a new selective and dual-acting antidepressant. 1650 14

Over two thirds of people suffering from depression complain of pain with or without reporting psychological symptoms. Physical symptoms are more prevalent among the women, the elderly, the poor, and in children population. Successful treatment of depression in children complicated by pain symptoms constitutes a great clinical challenge. Duloxetine has already emerged as a safe and effective treatment option for adult depressed patients with painful physical symptoms. However, no data exist in literature which suggests use of duloxetine in childhood and adolescent population for the same clinical indication. We report a case documenting successful use of duloxetine in a depressed girl child who also had severe pain and dissociative symptoms.
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PMID:Duloxetine for childhood depression with pain and dissociative symptoms. 1673 64

Duloxetine has demonstrated efficacy for the treatment of major depressive disorder (MDD) at a dose of 60 mg/day (given once daily). Whereas the target dose for the majority of patients is 60 mg/day, higher duloxetine doses (up to 120 mg/day) have been studied using a twice-daily dosing schedule. To further investigate the pharmacological profile of duloxetine within a once-daily dosing regimen at doses above 60 mg, we examined the safety and tolerability of duloxetine during a dose escalation from 60 mg/day to 120 mg/day. This single-arm, non-placebo-controlled study incorporated a 7-week dose escalation phase, in which patients and investigators were blinded as to timing of dose increases, followed by an open-label extension phase of up to 2 years duration. Patients (age >or=18 years) meeting DSM-IV criteria for MDD (n=128) received placebo for 1 week, followed by duloxetine (60 mg/day) titrated after 1 week to 90 mg/day, and after a further week to 120 mg/day. The dose of 120 mg/day was then maintained for 4 weeks. The extension phase comprised an initial 6-week dose stabilization period, during which duloxetine was tapered to the lowest effective dose, followed by continuation therapy at the stabilized dose. We assessed safety using spontaneously reported treatment-emergent adverse events (TEAEs), changes in vital signs, electrocardiograms (ECGs), laboratory analytes, and visual analogue scales (VAS) for gastrointestinal (GI) disturbance. Efficacy measures included the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score, the Clinical Global Impression of Severity (CGI-S) and Patient Global Impression of Improvement (PGI-I) scales, and VAS assessments of pain severity and interference. The rate of discontinuation due to adverse events during the acute phase of the study was 15.6%. The most frequently reported TEAEs were nausea, headache, dry mouth, dizziness, and decreased appetite. The majority of TEAEs were associated with initial duloxetine dosing; further escalations in dose produced few additional adverse events. VAS measures of GI disturbance worsened significantly compared with baseline values after 1 week of duloxetine treatment. Subsequent assessments of GI disturbance, following dose escalation to 90 mg/day and 120 mg/day, showed either no significant difference or a significant improvement from baseline. Significant improvements (P<.001) were observed in all assessed depression efficacy measures, and in five of six VAS pain outcomes, during acute phase treatment. During 2 years of extension phase therapy, the rate of discontinuation due to adverse events was 11.9%, and the only TEAEs reported by >10% of patients were upper respiratory tract infection (13.1%), headache (10.7%), and insomnia (10.7%). Mean changes from baseline to the end of the extension phase in supine systolic and diastolic blood pressure were 3.8 and 0.5 mm Hg, respectively, and there were no reports of sustained hypertension. Mean increase in heart rate was 5.9 bpm, while patients exhibited a mean weight increase of 3.1 kg over 2 years of treatment. Results from this study suggest that rapid dose escalation of duloxetine (60 mg/day --> 90 mg/day --> 120 mg/day) is safe and tolerable. Despite weekly escalation, the majority of adverse events were mild and transient and occurred in the first week of duloxetine dosing (at 60 mg once daily). Long-term treatment at a stabilized duloxetine dose was associated with a relatively low incidence of TEAEs and treatment discontinuation due to adverse events. Time course profiles of body weight and heart rate showed modest increases during 2 years of treatment [ClinicalTrials.gov number, NC T000 42575].
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PMID:Duloxetine for the treatment of major depressive disorder: safety and tolerability associated with dose escalation. 1684 41

Intradermal capsaicin injection produces immediate spontaneous pain behaviors, and a secondary mechanical hypersensitivity (SMH) that is employed in the clinic as a model potentially predictive of human neuropathic pain. Presently, we have characterized capsaicin-induced SMH in rats, and compared pharmacological actions of standard analgesics in this and two nerve injury models, the L5/L6 spinal nerve ligation (SNL) and sciatic nerve chronic constriction injury (CCI) models. Intraplantar capsaicin produced dose-related SMH (enhanced paw withdrawal response to von Frey monofilament stimulation at an area away from injection site) that lasted for over 4 h. While pretreatment with a potent selective transient receptor potential vanilloid receptor-1 (TRPV1) antagonist A-425619 (1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea) prevented development of acute nocifensive (flinching) behavior immediately following capsaicin injection (ED(50)=4.9 mg/kg), the compound failed to attenuate the SMH when administered 2 h following capsaicin (10 microg/10 microl). Additional standard analgesics were also tested 3 h following intraplantar capsaicin in the SMH model. Comparison of their potencies in attenuating mechanical hypersensitivity in capsaicin, SNL and CCI models revealed similar ED(50)s for morphine (2.3 mg/kg, 1.6 mg/kg and 3.2 mg/kg, respectively), gabapentin (33.1 mg/kg, 33.9 mg/kg and 26.3 mg/kg, respectively) and lamotrigine (9.1 mg/kg, 8.9 mg/kg and 15.5 mg/kg, respectively). Duloxetine produced 50-65% effect at the highest tested dose (50 mg/kg), whereas the highest tested doses of morphine (10 mg/kg), gabapentin (85.5 mg/kg) and lamotrigine (30 mg/kg) all produced >70% efficacy in capsaicin SMH, SNL and CCI models. In contrast, celecoxib and ibuprofen showed weak effects in all three models. All standard analgesics generally had weak efficacy in attenuating capsaicin-induced immediate acute flinching behavior when administered before capsaicin. These results provide further support to the suggestions that distinct pharmacological mechanisms underlie capsaicin-induced acute nocifensive and SMH behaviors, and certain neuronal mechanisms underlying neuropathic pain states are also contributory to capsaicin-induced SMH.
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PMID:Comparison of antinociceptive actions of standard analgesics in attenuating capsaicin and nerve-injury-induced mechanical hypersensitivity. 1696 19

(1) Several classes of antidepressants are available. The main difference between these classes is in their short-term pharmacological effects, leading to different patterns of adverse effects. Some antidepressants, especially tricyclics, have positive risk-benefit balances in the treatment of diabetic neuropathy. (2) Duloxetine, a compound chemically related to fluoxetine, appears to have a short-term mechanism of action similar to that of venlafaxine. In the European Union, duloxetine was first approved for female urinary stress incontinence. Another brand of duloxetine has since been marketed for depression and neuropathic pain in diabetic patients. (3) Duloxetine at a dose of 60 mg once a day showed moderate efficacy in 2 placebo-controlled trials. At this dose, however, there are no other comparative trials. It is therefore not possible to know whether duloxetine is as effective as other antidepressants. (4) Two placebo-controlled trials involving patients with pain due to diabetic neuropathy concluded that a dose of 60 mg/day had efficacy, although of doubtful clinical relevance. In the absence of comparative trials, however, we do not know if this efficacy is even equivalent to that of a tricyclic antidepressant used as an analgesic. (5) In fibromyalgia, a controversial clinical diagnosis, two double-blind placebo-controlled trials involving 207 and 354 patients failed to prove that duloxetine had tangible analgesic efficacy. It is therefore appropriate that this use is not mentioned in the "Indications" section of the summary of product characteristics (SPC). (6) The assessment of duloxetine in depression and neuropathic pain confirms existing data on its gastrointestinal, neuropsychological and hepatic adverse effects. In these trials, duloxetine increased blood pressure in a dose-dependent manner. (7) Duloxetine is metabolized by cytochrome P450 isoenzymes CYP 1A2 and CYP 2D6, creating an important risk of interactions with other drugs. (8) In practice, duloxetine currently has no place in the treatment of depression or diabetic neuropathy. Its efficacy has not yet been demonstrated to be even equivalent to that of other available drugs, and it has too many adverse effects, given this degree of uncertainty.
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PMID:Duloxetine: new indication. Depression and diabetic neuropathy: too many adverse effects. 1712 Dec 11


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